This project has developed a clinically useful method (laser Doppler instrument and its theory of operation) for clinical measurements of microcirculatory blood flow, the density of flowing red blood cells (RBCs), and mean RBC velocity. Assistance has been given to the commercialization of this methodology and its application to clinical research. Our clinical studies have been directed toward examining normal and abnormal microvascular dynamics through noninvasive clinical studies of skin and nasal mucosa, and toward intraoperative clinical studies of muscle and the CNS. Considerable theoretical work has been directed toward an adequate construct with which to interpret the physical measurements, and to refining the accuracy of the microcirculatory measurements. We have discovered abnormal microcirculatory patterns and responses in the skin of patients with sickle-cell disease, hypertension, certain cardiac circulatory syndromes, diabetes, and skin cancer. The microcirculatory effects of therapy are monitored with this technique, affording a better understanding of the microcirculatory components of these diseases.